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Publication Metadata only A new dataset of non-redundant protein/protein interfaces(Biophysical Society, 2003) Tsai, CJ; Wolfson, H; Nussinov, R; Department of Chemical and Biological Engineering; Keskin, Özlem; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 26605Publication Metadata only A new dataset of protein-protein interfaces(Cell Press, 2007) Güney, Emre; Nussinov, Ruth; Tsai, C. J.; Department of Computer Engineering; Department of Chemical and Biological Engineering; Gürsoy, Attila; Keskin, Özlem; Tunçbağ, Nurcan; Faculty Member; Faculty Member; PhD Student; Department of Computer Engineering; Department of Chemical and Biological Engineering; College of Engineering; College of Engineering; 8745; 26605; 245513Publication Metadata only A structured mechanical risk sensitivity assessment system using red cell deformability and fragmentation parameters(Ios Press, 2021) Yalçın, Özlem; Uğurel, Elif; Göktaş, Polat; Göksel, Evrim; Çilek, Neslihan; Atar, Dila; Faculty Member; Researcher; Researcher; PhD Student; PhD Student; Undergraduate Student; School of Medicine; School of Medicine; School of Medicine; Graduate School of Health Sciences; Graduate School of Health Sciences; School of Medicine; 218440; N/A; N/A; N/A; N/A; N/AN/APublication Metadata only Activation of protein kinase a cascade increases deformability of sickle red blood cells(Ios Press, 2021) Connes, Philippe; Boisson, Camille; Renoux, Celine; Gauthier, Alexandra; Fort, Romain; Nader, Elie; Poutrel, Solene; Göksel, Evrim; Yalçın, Özlem; PhD Student; Faculty Member; School of Medicine; School of Medicine; N/A; 218440Publication Metadata only Applications of deep learning to the assessment of red blood cell deformability(IOS Press, 2021) Turgut, Alper; N/A; Yalçın, Özlem; Faculty Member; School of Medicine; 218440BACKGROUND: Measurement of abnormal Red Blood Cell (RBC) deformability is a main indicator of Sickle Cell Anemia (SCA) and requires standardized quantification methods. Ektacytometry is commonly used to estimate the fraction of Sickled Cells (SCs) by measuring the deformability of RBCs from laser diffraction patterns under varying shear stress. In addition to estimations from model comparisons, use of maximum Elongation Index differences (Delta EImax) at different laser intensity levels was recently proposed for the estimation of SC fractions. OBJECTIVE: Implement a convolutional neural network to accurately estimate rigid-cell fraction and RBC concentration from laser diffraction patterns without using a theoretical model and eliminating the ektacytometer dependency for deformability measurements. METHODS: RBCs were collected from control patients. Rigid-cell fraction experiments were performed using varying concentrations of glutaraldehyde. Serial dilutions were used for varying the concentration of RBC. A convolutional neural network was constructed using Python and TensorFlow. RESULTS and CONCLUSIONS: Measurements and model predictions show that a linear relationship between Delta EImax and rigid-cell fraction exists only for rigid-cell fractions less than 0.2. The proposed neural network architecture can be used successfully for both RBC concentration and rigid-cell fraction estimations without a need for a theoretical model.Publication Metadata only Assessment of oxidant susceptibility of red blood cells in various species based on cell deformability(IOS Press, 2011) Simmonds, Michael J.; Meiselman, Herbert J.; Marshall-Gradisnik, Sonya M.; Pyne, Michael; Kakanis, Michael; Keane, James; Brenu, Ekua; Christy, Rhys; Başkurt, Oğuz Kerim; Faculty Member; School of Medicine; N/APublication Open Access Binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies(BioMed Central, 2007) Keskin, Özlem; Faculty Member; Faculty Member; The Center for Computational Biology and Bioinformatics (CCBB); College of Engineering; 26605Background: How antibodies recognize and bind to antigens can not be totally explained by rigid shape and electrostatic complimentarity models. Alternatively, pre- existing equilibrium hypothesis states that the native state of an antibody is not defined by a single rigid conformation but instead with an ensemble of similar conformations that co-exist at equilibrium. Antigens bind to one of the preferred conformations making this conformation more abundant shifting the equilibrium. Results: Here, two antibodies, a germline antibody of 36 - 65 Fab and a monoclonal antibody, SPE7 are studied in detail to elucidate the mechanism of antibody-antigen recognition and to understand how a single antibody recognizes different antigens. An elastic network model, Anisotropic Network Model (ANM) is used in the calculations. Pre- existing equilibrium is not restricted to apply to antibodies. Intrinsic fluctuations of eight proteins, from different classes of proteins, such as enzymes, binding and transport proteins are investigated to test the suitability of the method. The intrinsic fluctuations are compared with the experimentally observed ligand induced conformational changes of these proteins. The results show that the intrinsic fluctuations obtained by theoretical methods correlate with structural changes observed when a ligand is bound to the protein. The decomposition of the total fluctuations serves to identify the different individual modes of motion, ranging from the most cooperative ones involving the overall structure, to the most localized ones. Conclusion: Results suggest that the pre- equilibrium concept holds for antibodies and the promiscuity of antibodies can also be explained this hypothesis: a limited number of conformational states driven by intrinsic motions of an antibody might be adequate to bind to different antigens.Publication Metadata only Biomolecular systems interactions, dynamics, and allostery: reflections and new directions(Cell Press, 2015) Dyson, Jane; Bahar, Ivet; Department of Chemical and Biological Engineering; Keskin, Özlem; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 26605Publication Open Access Causality, transfer entropy, and allosteric communication landscapes in proteins with harmonic interactions(Wiley, 2017) Department of Chemical and Biological Engineering; Hacısüleyman, Aysima; Erman, Burak; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; N/A; 179997A fast and approximate method of generating allosteric communication landscapes in proteins is presented by using Schreiber's entropy transfer concept in combination with the Gaussian Network Model of proteins. Predictions of the model and the allosteric communication landscapes generated show that information transfer in proteins does not necessarily take place along a single path, but an ensemble of pathways is possible. The model emphasizes that knowledge of entropy only is not sufficient for determining allosteric communication and additional information based on time delayed correlations should be introduced, which leads to the presence of causality in proteins. The model provides a simple tool for mapping entropy sink-source relations into pairs of residues. By this approach, residues that should be manipulated to control protein activity may be determined. This should be of great importance for allosteric drug design and for understanding the effects of mutations on function. The model is applied to determine allosteric communication in three proteins, Ubiquitin, Pyruvate Kinase, and the PDZ domain. Predictions are in agreement with molecular dynamics simulations and experimental evidence.Publication Open Access Cloning, expression, purification, crystallization and X-ray analysis of inositol monophosphatase from Mus musculus and Homo sapiens(Wiley, 2012) Singh, Nisha; Halliday, Amy C.; Knight, Matthew; Lowe, Edward; Churchill, Grant C.; Lack, Nathan Alan; Faculty Member; School of Medicine; 120842Inositol monophosphatase (IMPase) catalyses the hydrolysis of inositol monophosphate to inositol and is crucial in the phosphatidylinositol (PI) signalling pathway. Lithium, which is the drug of choice for bipolar disorder, inhibits IMPase at therapeutically relevant plasma concentrations. Both mouse IMPase 1 (MmIMPase 1) and human IMPase 1 (HsIMPase 1) were cloned into pRSET5a, expressed in Escherichia coli, purified and crystallized using the sitting-drop method. The structures were solved at resolutions of 2.4 and 1.7 angstrom, respectively. Comparison of MmIMPase 1 and HsIMPase 1 revealed a core r.m.s. deviation of 0.516 angstrom.